Yang Min,Lu Xiaoluan,Tang Luyang,Fu Yangyang,Yang Peixin
The purpose of this work was first to propose a thermosensitive hydrogel incorporating Zn phthalocyanine loaded mixed micelles for drug delivery. The mixed micelles was prepared easily by dialysis method and the thermosensitive hydrogel was prepared by “cold method” using Pluronic F127 as hydrogel matrix. The properties of sol and gel transition caused by F127 temperature response enables the drug loaded micellar hydrogel(DLM-Gel) to gel in situ gelification upon injection providing long-term retention within the tumor. Sodium deoxycholate (SDC) and D-alpha tocopheryl polyethylene glycol succinate (TPGS) were utilized as micelles materials. Micelles resulted in a mean particle size around 106 nm, spherical morphology and loading efficiency up to 92%. The DLM-Gel displayed a three-dimensional network structure, which helps to stabilize ZnPc molecules because it can reduce the rotation and intermolecular collision of the ZnPc molecules, leading to the enhancement of fluorescence intensity and 1 O 2 generation. The production of 1 O 2 from DLM-Gel was more efficient than micelles under the same laser irradiation condition. The DLM-Gel was more photostable than free ZnPc and micelles in the timescale typically used in photodynamic therapy(PDT), only a small photobleaching event(16.91%) was observed after 20 min of light irradiation. Rheology studies demonstrated that DLM-Gel has the potential to be injected at room temperature and to adapt to the deformation of surrounding tissues during human motion. The in vitro drug release studies of DLM-Gel demonstrated slower drug release than mixed micelles. Phototoxicity experiments in A549 cells showed that DLM-Gel had significante toxicity.Therefore the injective micellar hydrogels is a potential drug delivery system for PDT.
Aim: High-dose administration of etoposide (VP16) was limited by its poor aqueous solubility and severe systemic toxicity on lymphoma therapy. Herein, a novel VP16-loaded lipid-based nanosuspensions (VP16-LNS) was developed for improving drug solubility, enhancing antitumor effect and reducing systemic toxicity. Materials & methods: VP16-LNS with soya lecithin and D-α-tocopheryl PEG 1000 succinate (TPGS) as stabilizers were prepared by nanoprecipitation method. Results: VP16-LNS exhibited uniform spherical morphology, small particle size and favorable colloidal stability. The concentration of VP16 in VP16-LNS was high enough (1017.67 μg/ml) for high-dose therapy on lymphoma. Moreover, VP16-LNS displayed long blood circulation time, selective intratumoral accumulation, remarkable antitumor effect and upregulated safety. Conclusion: VP16-LNS would be an efficient nanoformulation for clinical intravenous application against lymphoma.
Wenxiu Hou,Xin Zhao,Xiaoqing Qian,Fei Pan,Chunlei Zhang,Yuming Yang,Jesús Martínez de la Fuente,Daxiang Cui
The development of visual tumor theranostic nanoparticles has become a great challenge. In this study, D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) was conjugated to acid-sensitive cis-aconitic anhydride-modified doxorubicin (CAD) to obtain pH-sensitive anti-tumor prodrug nanoparticles (TCAD NPs) via self-assembling. Subsequently, the photosensitizer chlorin e6 (Ce6) was loaded into the resulting prodrug nanoparticles to prepare a novel tumor near-infrared fluorescence imaging and chemo–photodynamic combination therapy system (TCAD@Ce6 NPs). An accelerated release of doxorubicin (DOX) and chlorin e6 (Ce6) from the TCAD@Ce6 NPs could be achieved due to the hydrolysis of the acid-sensitive amide linker under mild acidic conditions (pH = 5.5). An in vitro experiment showed that A549 lung cancer cells exhibited a significantly higher uptake of DOX and Ce6 by using our delivery system than the free form of DOX and Ce6. An in vivo experiment showed that TCAD@Ce6 NPs displayed better tumor targeting gathering through the enhanced permeability and retention (EPR) effect than free Ce6, thus improving fluorescence imaging. Moreover, the chemo–photodynamic combination therapy of TCAD@Ce6 NPs combined with near-infrared laser irradiation was confirmed to be capable of inducing high apoptosis and necrosis of tumor cells (A549) in vitro and to display a significantly higher tumor growth suppression in the A549 lung cancer-bearing mice model. Furthermore, compared with exclusive chemotreatment (DOX) or photodynamic treatment (Ce6), our system showed enhanced therapeutic effects both in vitro and in vivo. In conclusion, the high performance TCAD@Ce6 NPs can be used as a promising NIR fluorescence imaging and highly effective chemo–photodynamic system for theranostics of lung cancer, etc. in the near future.
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